Suppression of matrix metalloproteinase-2-mediated cell invasion in U87MG, human glioma cells by anti-microtubule agent: in vitro study.
Because microtubules are important components of cell motility and intracellular transport, it is reasonable to propose that the depolymerizing effect of an antimicrotubule agent, estramustine, on glioma microtubules would modulate cell invasiveness. To determine whether matrix metalloproteinases, key factors in cell invasion, are affected by exposure to estramustine, a cell proliferation assay, a zymogram, a collagenolysis assay and a haptoinvasion assay were used in this study. The zymogram revealed that an activated (62 kDa) form of matrix metalloproteinase-2 diminished with increasing estramustine concentrations. The collagenolysis assay demonstrated approximately 2.5- to 21-fold lower rates of enzymatic activity suppressed by estramustine in a dose-dependent manner at estramustine concentrations of 1, 5, and 10 microM, compared with the control group. On the haptoinvasion assay, no statistically significant difference was seen in the 0.5 microM estramustine group, whereas 1-10 microM estramustine groups revealed significant suppression of invasion from 6 to 24 h in a dose-dependent manner. The results suggest that estramustine suppresses the invasion of U87MG cells in vitro using the decreasing available matrix metalloproteinase-2, an effect caused by the disassembly of microtubules. Suppression of the infiltrative capacity of malignant glioma cells could be of significant value in the treatment of this disease.
Yoshida
D
D
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan.
Piepmeier
J M
JM
Bergenheim
T
T
Henriksson
R
R
Teramoto
A
A
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D004961:Estramustine / Q000494:pharmacology*; D018093:Gelatinases / Q000037:antagonists & inhibitors*; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008870:Microtubules / Q000187:drug effects / Q000502:physiology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*
D018906:Antineoplastic Agents, Alkylating; D009363:Neoplasm Proteins; D004961:Estramustine; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2